Tolterodine is an anti-muscaranic agent used in the treatment of patients with overactive bladder. Tolterodine Tartrate is currently available as film coated tablets containing 1 mg or 2 mg of the active and also as extended release capsules containing 2 mg or 4 mg of the active. Dry mouth is major side effect associated with tolterodine. To substantially minimize the impact of the side effect, it is desirable to administer tolterodine in extended release dosage form to reduce the frequency of administration and to reduce the frequency of side effects as compared to an immediate release dosage form.
WO0027364, WO03053428, WO0134139 EP1128819, EP1227806, U.S. Pat. No. 6,911,217, U.S. Pat. No. 6,770,295 and U.S. Pat. No. 6,630,102 disclose controlled release beads comprising a core unit of a substantially water soluble or water swellable inert material, a first layer of substantially water insoluble polymer on the core unit, a second layer containing an active ingredient and hydroxypropylmethylcellulose (polymer) as binder covering the first layer and a third layer of polymer on the second layer, wherein the first layer is adapted to control water penetration into the cores. The third layer of polymer is effective for controlled release of the active ingredient.
WO2004/105735, EP1635795, WO2007/029087 disclose a controlled release pharmaceutical composition of tolterodine comprising of one or more coated units, wherein each coated unit comprises a core, a first layer surrounding atleast a portion of the core, the first layer comprising tolterodine and one or more hydrophilic polymers and a second layer surrounding atleast a portion of the first layer and comprising one or more polymers effective for controlled release of the tolterodine from the first layer.
WO2006/021425 and EP1781275 disclose a sustained release composition comprising a core element coated with an outer layer comprising a hydrophobic sustained release polymer. The core element is selected from (i) an inert core with a first layer comprising of tolterodine and a binder and (ii) a matrix core formulation containing a matrix core material, tolterodine and a binder. The binder is preferably selected from polymers such as hydroxypropylmethylcellulose, hydroxypropylcellulose and polyvinylpyrrolidone.
WO2007/122015 discloses a controlled release tolterodine beads comprising a sugar core, an innermost sealcoat layer comprising hydroxypropylmethylcellulose, a drug layer comprising tolterodine and a hydrophilic polymer and an outer control release layer. The thickness of the hydrophilic hydroxypropylmethylcellulose sealcoat layer helps to modulate the release of tolterodine.
EP1839649 discloses a sustained release pharmaceutical composition comprising a) a coat comprising at least one water insoluble permeable polymer and at least one water soluble polymer applied onto b) pellets containing only tolterodine and microcrystalline cellulose (polymer).
It is evident from the prior art that in all formulations, a polymer is necessarily used in combination with the drug. For example:    i) the drug layer containing tolterodine and binder (polymer) is in between the two layers containing water insoluble polymer as in WO0027364, WO03053428, WO0134139, EP1128819, EP1227806, U.S. Pat. No. 6,911,217, U.S. Pat. No. 6,770,295 and U.S. Pat. No. 6,630,102; or    ii) the drug layer containing tolterodine and a hydrophilic polymer is in between the innermost sealcoat layer comprising hydroxypropylmethylcellulose and outer control release layer as in WO2007/122016; or    iii) the drug layer comprising tolterodine and one or more hydrophilic polymer is coated with one or more polymers as in WO2004/105735, EP1635795 and WO2007/029087; or    iv) the drug layer comprising tolterodine and a binder (binder selected from group consisting of cellulose derivative and polyvinyl pyrrolidone, both being polymer) is coated with hydrophobic sustained release polymer as in WO2006/021425 and EP1781275; or    v) the drug core containing only tolterodine and microcrystalline cellulose (polymer) is coated with at least one water insoluble permeable polymer and at least one water soluble polymer as in EP1839649.